Showing papers by "Chang Hwa Jung published in 2011"

ULK1 inhibits the kinase activity of mTORC1 and cell proliferation.

Abstract: ULK1 (Unc51-like kinase, hATG1) is a Ser/Thr kinase that plays a key role in inducing autophagy in response to starvation. ULK1 is phosphorylated and negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1). Previous studies have shown that ULK1 is not only a downstream effector of mTORC1 but also a negative regulator of mTORC1 signaling.1–3 Here, we investigated how ULK1 regulates mTORC1 signaling, and found that ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Deficiency or knockdown of ULK1 or its homolog ULK2 enhanced mTORC1 signaling, cell proliferation rates and accumulation of cell mass, whereas overexpression of ULK1 had the opposite effect. Knockdown of Atg13, the binding partner of ULK1 and ULK2, mimicked the effects of ULK1 or ULK2 deficiency or knockdown. Both insulin and leucine stimulated mTORC1 signaling to a greater extent when ULK1 or ULK2 was deficient or knocked down. In contrast, Atg5 deficiency did not have a significant effect on mTORC1 signaling and cell proliferation. The stimulatory effect of ULK1 knockdown on mTORC1 signaling occurred even in the absence of tuberous sclerosis complex 2 (TSC2), the negative regulator of mTORC1 signaling. In addition, ULK1 was found to bind raptor, induce its phosphorylation, and inhibit the kinase activity of mTORC1. These results demonstrate that ULK1 negatively regulates the kinase activity of mTORC1 and cell proliferation in a manner independent of Atg5 and TSC2. The inhibition of mTORC1 by ULK1 may be important to coordinately regulate cell growth and autophagy with optimized utilization of cellular energy.

Anti-inflammatory effect of Rhus verniviflua Stokes by suppression of iNOS-mediated Akt and ERK pathways: in-vitro and in-vivo studies.

Abstract: Objectives Rhus verniciflua Stokes (RVS), which has valuable medicinal properties, has for many years been prescribed for inflammation in east Asian medicine. Recent studies suggest that RVS has potent antioxidative, antitumor and anti-inflammatory properties. Methods In this study, the anti-inflammatory effects of RVS in vitro and in vivo were investigated. The ethanol extract from RVS was partitioned with different solvents in order of increasing polarity. Key findings Among the various extracts, the n-butanol extract displayed the most potent activity against nitric oxide and reactive oxygen species. The n-butanol extract also significantly regulates expression of nitric oxide synthase, which inhibits nitric oxide production at the transcriptional level in activated macrophages. Immunoblot analysis also showed that n-butanol extract suppresses the phosphorylation of extracellular signal-regulated kinase and Akt, suggesting that nitric oxide synthase suppression might be mediated via the extracellular signal-regulated kinase and Akt signaling pathways. This study also investigated whether n-butanol exerts an anti-inflammatory effect in an animal model. n-butanol extract significantly reduces carrageenan-induced mouse paw edema at 5 h. Conclusions These results suggest that RVS could be a promising candidate agent for inflammation prevention and combination therapy with anti-inflammatory drugs.